Investigating the Regulatory Role of PKR in Systemic Inflammation Triggered Neuroinflammation and its Role in Cholinergic Neurons in Modulating Cognitive Functions

Background Double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and the formation of inflammasomes. Meanwhile, PKR in neurons helps mediate stress Aß to trigger apoptosis affects cognitive functions. This study aims at investigating whether can be pharmacological target prevent systemic inflammation-triggered neuroinflammation dysfunctions. Method The experimental model laparotomy adopted address inflammation initiated surgery. Male C57BL/6J PKR-KO mice were divided into two groups: control group under sevoflurane anesthesia anesthesia. Cytokine mRNA expression tissues was examined quantitative RT-PCR. Behavioral tests performed examine effects on Furthermore, role cholinergic neurons, stereotaxic injection dominant negative AAV-DIO-PKR-K296R right lateral ventricle Rosa-ChAT-IRES-Cre inhibit neurons. Result Our preliminary showed induced neural male mice. At 4 h one day after laparotomy, genetic knockout potently downregulated elevated IL-1ß generated both liver frontal brain. Additonally, impairment observed wild type following terms decline problem-solving abilities, impaired short-term long term memory puzzle box test; reduced recognition novel object spatial working spontaneous Y-maze; while for mice, flexibility, remained intact laparotomy. weeks AAV-DIO-PKR-K296R, significant reduction p-PKR level It implies AAVcan phosphorylation Conclusion reveals could attenuate inflammation, neuroinflammation, impairment.Further studies will effect Acknowledgement:The supported General Research Fund (17123217) RCCC.